Quinine salts of hydroxyphenyl-arsonic acids and process for making same



Patented Feb. 28, 1928.

Eif'i'ES intact WALTER KARREB, OF BASEL, SWITZERLAND, ASSEGNOR TO THE HOFFMAN N-LA ROCHE CHEMICAL \VORKS, 0F NEVV YORK, N. Y., A COR-FORATION OF NEW YORK.

QUININE SALTS OF HYDROXYPHENYL-ARSONIC ACIDS AND PRQCESS FOR MAKING SAME.

No Drawing. Application filed July 22; 1926, Serial No. 124,295, and in Switzerland November 6, 1925.

The quinine salts of hydroxyphenyl-arsonic acids, which possess valuable therapeutic properties in the treatment of tropical diseases such as malaria, dysentery, etc., are characterized by easy crystallization. They are rather difficultly soluble in cold, more easily soluble in hot Water. They further dissolve in alcohol and dilute mineral acids. The aqueous solutions react neutrally With litmus. By adding alkali quinine is precipitated. They are to be used as 1nedicines. v

The quinine salts of hydroxyphenyl-arsonic acids are obtained by treating the free hydroxyphenyl-arsonic acids with quinine or the salts of hydroxyphenyl-arsonic acids With soluble quinine salts. By hydroxyphenylarsonic acids I mean compounds containing as substituents only the hydroxyl group and the arsonic acid group.

Example 1.

2.85 parts of the mono-sodium salt of para-hydroxyphenyl-ars0nic acid are dissolved in tenfold the quantity of Water and to this is added a solution of 3.96 parts of quinine chlorhydrate in thirtyfold the quantity ofwater. A thick precipitate is thereby produced. This precipitate is separated from the mother liquor and the salt thus obtained is dissolved in hot Water andthen recrystallized. The quinine salt of parahydroXyphenyl-arsonic acid crystallizes in fine CGOlOXlGSS needles Which melt, at 177- 178 The following graphical formula illustrates the reaction Which takesplace:

EEO/(L \n cikonr Ha AsOzHNa H cn on)-H H2 1101+ N I Quininechlorhydrate AH Monosodium salt of V N p-hydroxyphenylarsonic acid 'Q I OH ml/ I \n-cikom CHi c11 o11 -11 I H; As\0 Hz l N HgCO I AHv Quinine salt of p-hydroxyphenylarsonic acid.

Example 2. 2.18 parts of para-liydroxyphenyl-arsenic acid ancFSFEi parts of quinine are heated in thirty-fold the quantlty of Water during 8 hours inthe Water-bath. Upon cooling the quinine salt of hydroxyphenyl-arsonic acid 1s precipitated in fine needles. After dissolving these needles in hot Water and effect ing ire-crystallization, the same salt is obtamed as the one described 1n Example 1.

The following graphical formula illus trates the reaction whichtake place:

Quinine salt of p-hydroxyphenylarsonic acid It is obvious from the above examples and torinulze that the acid and the quinine coinb11 16 1n the same way whether both are tree or both are present in the form of their salts;

in fact, when, for instance, mono-sodium salt ofpara hydroxyphenyl-arsonic acid is treated with quinine chlorhydrate as in Example 1, sodium chloride is first formed, leaving the free acid and the free quinine to react with one another, just as do the free acid and the free quinine in Example 2, so that even it the salts are brought together the reaction 'is really one between the free acid and the free quinine. Therefore, when I speak in my claims of permitting the acid to react with the quinine, I intend to include in such expression not only the reaction between the free acid and the tree quinine, but also the reaction between their respective salts.

I claim:

1. As new articles of manufacture the quinine salts of hydroxyphenyl-arsonic acids which may be obtained by treating hydroxyphenyl-arsonic acids with quinine or the salts of hydroxyphcnyl-arsonic acids with soluble quinine salts,said acids containing as substituents only the hydroxyllgroup and the arsonic acid group, the newsalts possessing valuable therapeutic properties, being characterized by easy crystallization, dissolving rather difiicultly in cold, more easily in hot water, being further soluble in alcohol and dilute mineral acids, the aqueous solutions reacting neutrally with litmus, the addition of alkali causing quinine to be precipitated. V

2. As a new article of manufacture the quinine salt of para-hydroxyphenol-arsonic acid which may be obtained by treating parahydroxyphenyl-arsonic acid with quinine or the salts ofpara-hydroxyphenyl-arsonic sold with soluble quinine salts, said acid containing as substituents only the hydroXylgroup and the arsonic acid group, the new salt possessing valuable therapeutic properties, melting at 177 1789 C.,being characterized by easy crystallization, dissolving rather diiiicultly in cold, more easily in hot water, being further soluble in alcohol and dilute mineral acids, the aqueous solution reacting neutrally with litmus, the addition of alkali causing quinine to be precipitated.

3: The process for the manufacture of quinine salts of hydroxyphenyl-arsonic acids which consists in allowing hydroxyphenylarsenic acids'containing as substituents only the hydroxyl group and the arsonic acid group to react with quinine.

4:. The process for the manufacture of quinine salts of hydroxyphenyl-arsonic acids which consists in allowing the free hydroxyphenyl arsonic acids containing as substituents only the hydroxyl group and the arsonic acid group to react with free quinine.

5. The process for the manufacture of quinine salts of hydroXyphenyl-arsonic acids which consists in allowing the salts of hydronyphenyl-arsonic acids containing as substituents only the hydroxyl group and the arsonic acid group to react with soluble quinine salts.

In witness whereof I have hereunto set my hand.

DR. WALTER KARRER. 

